This proposal is designed to assess the impact of selected estrogen, progestin and estrogen/progestin supplementation on cardiovascular disease risk factors, coagulation parameters and bone density and strength in peri- and postmenopausal women. The weight of the evidence currently suggests that unopposed estrogen supplementation lowers the risk of death from coronary heart disease (CHD), is effective at preventing bone loss and subsequent fracture, and is not associated with an increased risk of thrombogenesis, but increases the risk of endometrial cancer in women with intact uteri. Effects of estrogen/progestin or unopposed progestin supplementation on CHD risk factors and bone have not been clearly documented. Basic questions remain regarding 1) the effects of unopposed estrogen on CHD risk factors and bone in women using usual doses of estrogen replacement therapy; 2) the effects of adding a progestational agent to an estrogen replacement regimen on CHD risk factors and bone; and 3) the impact of unopposed progestin on CHD risk factors and bone. As part of a collaborative approach to the study of post- menopausal estrogen/progestin interventions, we propose to enroll, at minimum, 150 women aged 45 to 59 years in a randomized trial designed to assess the effect of selected estrogen, progestin and estrogen/progestin supplementation on lipids, lipoproteins, apoproteins, coagulation parameters, and bone densities. Based on modified factorial design, the trial will have six arms: (A) Oral estrogen and oral progestin; (B) Transdermal estrogen and oral progestin; (C) Oral progestin only; (D) Oral estrogen only; (E) Transdermal estrogen only; (F) Placebo Only hysterectomized women will be randomized to the unopposed estrogen arms (D & E). Participants will be followed for three years, and outcomes of interest will be assessed at specified times during the trial and at the final trial visit. The identification of a regimen which 1) provides favorable alterations in lipids and lipoproteins, 2) prevents bone loss, and 3) protects the endometrium of "at risk" women would be of significant benefit to the health and well being of all postmenopausal women.